Our previous research has demonstrated a significant effect of the hormonal contraceptive depot medroxyprogestrone acetate (DMPA) on weight and adipose gains in adolescent girls. My long-term career goal is to contribute substantially to our understanding of the mechanism for weight gain among adolescents on DMPA. My short term career objectives are to work closely with respected mentors to (i) increase my basic knowledge of fundamental and clinical pharmacology, (ii) increase my basic knowledge of reproductive endocrinology and physiology, (iii) develop an effective, integrated pharmacokinetic-pharmacodynamic model of DMPA, (iv) define the cellular effects of DMPA on the peripheral adipocyte, and (v) become proficient in grant preparation, data analysis and ethical conduct of research. These objectives will be achieved through strong mentorship and institutional commitment to the training goals and research plan. The multidisciplinary research environment offered by the affiliation of a large teaching hospital with a well-funded [unreadable] School of Medicine provides all the resources needed for career development and successful conduct of research. The proposed research will: 1) determine the relationship between circulating plasma MPA concentrations and weight gain in adolescent girls; 2) define the effects of DMPA on the expression of the progesterone receptor, lipoprotein lipase, and fatty acid synthase by the peripheral adipocyte; 3) define the relationship between the peripheral fat cell response and weight gain in adolescent girls, and 4) explore the role of the peripheral adipocyte cell response to DMPA as a potential mediator of the relationship between circulating plasma MPA concentrations and weight gain. The proposed study will provide information on the underlying mechanism of DMPA-associated weight gain. Results from the study will pave the way for future directions, i.e., tailoring DMPA to the individual user such that contraceptive efficacy is maintained and side effects are minimized. My long-term objective with the proposed training and research plan is to become a national leader on hormonal contraception in adolescents. [unreadable] [unreadable] [unreadable]